tbuckley/cabot-search huggingface dataset:
Circulating Extracellular Vesicle-Propagated microRNA Signature as a Vascular Calcification Factor in Chronic Kidney Disease
Authors: Takaaki Koide, Shintaro Mandai, Reo Kitaoka, Hisazumi Matsuki, Motoko Chiga, Kouhei Yamamoto, Kotaro Yoshioka, Yohsuke Yagi, Soichiro Suzuki, Tamami Fujiki, Fumiaki Ando, Takayasu Mori, Koichiro Susa, Soichiro Iimori, Shotaro Naito, Eisei Sohara, Tatemitsu Rai, Takanori Yokota, Shinichi Uchida
Journal: Circulation Research (2023)

Chronic kidney disease (CKD) accelerates vascular calcification via phenotypic switching of vascular smooth muscle cells (VSMCs). We investigated the roles of circulating small extracellular vesicles (sEVs) between the kidneys and VSMCs and uncovered relevant sEV-propagated microRNAs (miRNAs) and their biological signaling pathways.We established CKD models in rats and mice by adenine-induced tubulointerstitial fibrosis. Cultures of A10 embryonic rat VSMCs showed increased calcification and transcription of osterix (Sp7), osteocalcin (Bglap), and osteopontin (Spp1) when treated with rat CKD serum. sEVs, but not sEV-depleted serum, accelerated calcification in VSMCs. Intraperitoneal administration of a neutral sphingomyelinase and biogenesis/release inhibitor of sEVs, GW4869 (2.5 mg/kg per 2 days), inhibited thoracic aortic calcification in CKD mice under a high-phosphorus diet. GW4869 induced a nearly full recovery of calcification and transcription of osteogenic marker genes. In CKD, the miRNA transcriptome of sEVs revealed a depletion of 4 miRNAs, miR-16-5p, miR-17~92 cluster-originated miR-17-5p/miR-20a-5p, and miR-106b-5p. Their expression decreased in sEVs from CKD patients as kidney function deteriorated. Transfection of VSMCs with each miRNA-mimic mitigated calcification. In silico analyses revealed VEGFA (vascular endothelial growth factor A) as a convergent target of these miRNAs. We found a 16-fold increase in VEGFA transcription in the thoracic aorta of CKD mice under a high-phosphorus diet, which GW4869 reversed. Inhibition of VEGFA-VEGFR2 signaling with sorafenib, fruquintinib, sunitinib, or VEGFR2-targeted siRNA mitigated calcification in VSMCs. Orally administered fruquintinib (2.5 mg/kg per day) for 4 weeks suppressed the transcription of osteogenic marker genes in the mouse aorta. The area under the curve of miR-16-5p, miR-17-5p, 20a-5p, and miR-106b-5p for the prediction of abdominal aortic calcification was 0.7630, 0.7704, 0.7407, and 0.7704, respectively.The miRNA transcriptomic signature of circulating sEVs uncovered their pathologic role, devoid of the calcification-protective miRNAs that target VEGFA signaling in CKD-driven vascular calcification. These sEV-propagated miRNAs are potential biomarkers and therapeutic targets for vascular calcification.
Zolbetuximab Improves Survival in Gastric Cancer
Journal: Cancer Discovery (2023)

Results from the phase III SPOTLIGHT trial show that the investigational mAb zolbetuximab plus chemotherapy improves progression-free survival and overall survival in patients newly diagnosed with claudin 18.2-positive, HER2-negative locally advanced inoperable or metastatic gastric or gastroesophageal junction cancer. The drug could become a standard treatment option for these patients.
Chronic Kidney Disease Is Characterized by Expansion of a Distinct Proinflammatory Intermediate Monocyte Subtype and by Increased Monocyte Adhesion to Endothelial Cells
Authors: Sarah Cormican, Neema Negi, Serika D. Naicker, Md Nahidul Islam, Barbara Fazekas, Rachael Power, Tomás P. Griffin, M. Conall Dennedy, Briain MacNeill, Andrew F. Malone, Matthew D. Griffin
Journal: Journal of the American Society of Nephrology (2023)

CKD is accompanied by abnormal inflammation, which contributes to progressive loss of functional renal tissue and accelerated cardiovascular disease. Although studies have documented that dysregulation of monocyte maturation and function is associated with CKD and its complications, it is not well characterized. This study reveals that a distinctive human monocyte subtype with high propensity for releasing proinflammatory mediators and activating endothelial cells is increased in adults with CKD compared with adults with high cardiovascular risk and normal kidney function. It also demonstrates that human monocyte adhesion to endothelial layers and responses to specific inflammatory migration signals are enhanced in CKD. These findings offer insights into the mechanisms of CKD-associated intravascular and localized inflammation and may suggest potential targets for therapeutic interventions.
A Novel Creatinine Muscle Index Based on Creatinine Filtration: Associations with Frailty and Mortality
Authors: Shoshana H. Ballew, Linda Zhou, Aditya Surapaneni, Morgan E. Grams, B. Gwen Windham, Elizabeth Selvin, Josef Coresh, Shiyuan Miao, Lesley A. Inker, Andrew S. Levey
Journal: Journal of the American Society of Nephrology (2023)

Background Low muscle mass is related to frailty and increased mortality in older adults. However, muscle mass is not easily assessed in routine clinical practice. Methods This study describes a novel creatinine muscle index (CMI) on the basis of serum creatinine and cystatin C in a community-based sample of older adults from the Atherosclerosis Risk in Communities Study. Analyses included 4639 participants who attended visit 5 (2011–2013) and 12,786 participants who attended visit 2 (1990–1992). CMI was defined as creatinine filtration (the product of serum creatinine times eGFR on the basis of cystatin C) and was analyzed in sex-specific tertiles. Cross-sectional associations of CMI with a frailty trichotomy, defined by the number (robust [0]/prefrail [1–2]/frail [3–5]) of five frailty components (weight loss, slowness, exhaustion, weakness, and low physical activity), were studied using polychotomous logistic regression and binary logistic regression with each frailty component. Cox regression was used to estimate associations of CMI at visit 5 and visit 2 with mortality. Models were adjusted for demographics, clinical variables, and comorbid conditions. Results CMI (tertile 1 versus 3) was moderately associated with frailty (visit 5: adjusted odds ratio 4.23 [95% CI, 2.02 to 8.87] in men and 2.34 [95% CI, 1.41 to 3.89] in women) and with mortality (visit 5: adjusted hazard ratio 1.45 [95% CI, 1.08 to 1.94] in men and 1.55 [95% CI, 1.13 to 2.12] in women; similar results were seen at visit 2). Conclusion Lower CMI was associated with frailty and increased mortality, two clinical outcomes known to be associated with decreased muscle mass. Creatinine filtration may be an index of muscle mass and have utility in clinical practice, particularly at low levels.
Estimating Prognosis in Anti-Glomerular Basement Membrane Disease
Authors: Richard J. Glassock
Journal: Journal of the American Society of Nephrology (2023)

Department of Medicine, Geffen School of Medicine at UCLA, Los Angeles, California Correspondence: Dr. Richard J. Glassock, 3329 Bahia Blanca East, Unit B, Laguna Woods, CA 92637. Email: [email protected] See related article "Risk Stratification to Predict Renal Survival in Anti–Glomerular Basement Membrane Disease," on pages 505–514.
Local 5-HT signaling bi-directionally regulates the coincidence time window for associative learning
Authors: Jianzhi Zeng, Xuelin Li, Renzimo Zhang, Mingyue Lv, Yipan Wang, Ke Tan, Xiju Xia, Jinxia Wan, Miao Jing, Xiuning Zhang, Yu Li, Yang Yang, Liang Wang, Jun Chu, Yan Li, Yulong Li
Journal: Neuron (2023)
Campo E, Jaffe ES, Cook JR, et al. The International Consensus Classification of Mature Lymphoid Neoplasms: a report from the Clinical Advisory Committee. <i>Blood</i>. 2022;140(11):1229-1253.
Journal: Blood (2023)

In Figures 5A (page 3571) and 6A (page 3572), the same western blot was used for pFKHR and pERK detection.Therefore, both blots have the same loading control, AFX, which is correctly shown in Figure 6A.In 1 lane (MIP-1α, 5 minutes, wortmannin), Figure 5A includes an incorrect negative control.This is due to cutting of the wrong loading control lane.Since the correct loading control is shown in Figure 6A, the error does not impact the scientific message of the study.
Gold nanoparticles-embedded ceria with enhanced antioxidant activities for treating inflammatory bowel disease
Authors: Mingyi Li, Jia Liu, Lin Shi, Cheng Zhou, Meizhen Zou, Daan Fu, Ye Yuan, Chundong Yao, Lifang Zhang, Sumei Qin, Miaodeng Liu, Qian Cheng, Zheng Wang, Lin Wang
Journal: Bioactive Materials (2023)

The excessive reactive oxygen species (ROS) is a hallmark associated with the initiation and progression of inflammatory bowel disease (IBD), which execrably form a vicious cycle of ROS and inflammation to continually promote disease progression. Here, the gold nanoparticles-embedded ceria nanoparticles (Au/CeO2) with enhanced antioxidant activities are designed to block this cycle reaction for treating IBD by scavenging overproduced ROS. The Au/CeO2 with core-shell and porous structure exhibits significantly higher enzymatic catalytic activities compared with commercial ceria nanoparticles, likely due to the effective exposure of catalytic sites, higher content of Ce (III) and oxygen vacancy, and accelerated reduction from Ce (IV) to Ce (III). Being coated with negatively-charged hyaluronic acid, the Au/CeO2@HA facilitates accumulation in inflamed colon tissues via oral administration, reduces pro-inflammatory cytokines, and effectively alleviates colon injury in colitis mice. Overall, the Au/CeO2@HA with good biocompatibility is a promising nano-therapeutic for treating IBD.
Enrichment of oral-derived bacteria in inflamed colorectal tumors and distinct associations of Fusobacterium in the mesenchymal subtype
Authors: Brett S. Younginger, Oleg Mayba, Jens Reeder, Deepti R. Nagarkar, Zora Modrusan, Matthew L. Albert, Allyson L. Byrd
Journal: Cell Reports Medicine (2023)

While the association between colorectal cancer (CRC) features and Fusobacterium has been extensively studied, less is known of other intratumoral bacteria. Here, we leverage whole transcriptomes from 807 CRC samples to dually characterize tumor gene expression and 74 intratumoral bacteria. Seventeen of these species, including 4 Fusobacterium spp., are classified as orally derived and are enriched among right-sided, microsatellite instability-high (MSI-H), and BRAF-mutant tumors. Across consensus molecular subtypes (CMSs), integration of Fusobacterium animalis (Fa) presence and tumor expression reveals that Fa has the most significant associations in mesenchymal CMS4 tumors despite a lower prevalence than in immune CMS1. Within CMS4, the prevalence of Fa is uniquely associated with collagen- and immune-related pathways. Additional Fa pangenome analysis reveals that stress response genes and the adhesion FadA are commonly expressed intratumorally. Overall, this study identifies oral-derived bacteria as enriched in inflamed tumors, and the associations of bacteria and tumor expression are context and species specific.
Activity-balanced GLP-1/GDF15 dual agonist reduces body weight and metabolic disorder in mice and non-human primates
Authors: Yuanyuan Zhang, Xinyu Zhao, Xiaona Dong, Yuying Zhang, Haixia Zou, Yaoguang Jin, Wei Guo, Peng Zhai, Xu Chen, Alexei Kharitonenkov
Journal: Cell Metabolism (2023)
Immune checkpoint HLA-E:CD94-NKG2A mediates evasion of circulating tumor cells from NK cell surveillance
Authors: Xiaowei Liu, Jinen Song, Hao Zhang, Xinyu Liu, Fengli Zuo, Yunuo Zhao, Yujie Zhao, Xiaomeng Yin, Xinyu Guo, Xi Wu, Hu Zhang, Jie Xu, Jianping Hu, Jing Jing, Xuelei Ma, Hubing Shi
Journal: Cancer Cell (2023)
<i>CYP1A2</i> Genetic Variation, Coffee Intake, and Kidney Dysfunction
Authors: Sara Mahdavi, Paolo Palatini, Ahmed El-Sohemy
Journal: JAMA Network Open (2023)

Caffeine is detoxified by cytochrome P450 1A2 (CYP1A2), and genetic variation in CYP1A2 impacts the rate of caffeine clearance. Factors that may modify the association between coffee intake and kidney disease remain unclear.To assess whether CYP1A2 genotype modifies the association between coffee intake and kidney dysfunction.The Hypertension and Ambulatory Recording Venetia Study (HARVEST) was a prospective cohort study of individuals with stage 1 hypertension in Italy; HARVEST began on April 1, 1990, and follow-up is ongoing. The current study used data from April 1, 1990, to June 30, 2006, with follow-up of approximately 10 years. Blood pressure and biochemical data were collected monthly during the first 3 months, then every 6 months thereafter. Data were analyzed from January 2019 to March 2019. Participants were screened and recruited from general practice clinics. The present study included 1180 untreated participants aged 18 to 45 years with stage 1 hypertension; those with nephropathy, diabetes, urinary tract infection, and cardiovascular disease were excluded.Coffee intake and CYP1A2 genotype rs762551 were exposures analyzed over a median follow-up of 7.5 (IQR, 3.1-10.9) years.Albuminuria (defined as an albumin level of ≥30 mg/24 h) and hyperfiltration (defined as an estimated glomerular filtration rate of ≥150 mL/min/1.73 m2) were the primary outcomes as indicators of kidney dysfunction.Among 1180 participants, genotyping, lifestyle questionnaires, and urine analysis data were obtained from 604 individuals (438 [72.5%] male) with a mean (SD) age of 33.3 (8.5) years and a mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) of 25.4 (3.4). A total of 158 participants (26.2%) consumed less than 1 cup of coffee per day, 379 (62.7%) consumed 1 to 3 cups per day, and 67 (11.1%) consumed more than 3 cups per day. Genotype frequencies for rs762551 (260 participants [43.1%] with genotype AA, 247 participants [40.8%] with genotype AC, and 97 participants [16.1%] with genotype CC) did not differ between coffee intake categories. The level of risk of developing albuminuria, hyperfiltration, and hypertension, assessed by Cox regression and survival analyses, was not associated with coffee intake in the entire group or among fast metabolizers. The risks of albuminuria (adjusted hazard ratio [aHR], 2.74; 95% CI, 1.63-4.62; P < .001), hyperfiltration (aHR, 2.11; 95% CI, 1.17-3.80; P = .01), and hypertension (aHR, 2.81; 95% CI, 1.51-5.23; P = .001) increased significantly among slow metabolizers who consumed more than 3 cups per day.In this study, the risks of albuminuria, hyperfiltration, and hypertension increased with heavy coffee intake only among those with the AC and CC genotypes of CYP1A2 at rs762551 associated with slow caffeine metabolism, suggesting that caffeine may play a role in the development of kidney disease in susceptible individuals.
Estimation of Oncologic Surgery Case Volume Before and After the COVID-19 Pandemic in France
Authors: Christine Le Bihan-Benjamin, Mathieu Rocchi, Maxime Putton, Jean-Baptiste Méric, Philippe Jean Bousquet
Journal: JAMA Network Open (2023)

COVID-19 has had a major effect on health care activities, especially surgery. At first, comparisons were proposed using 2019 activities as the highest standard. However, while such an approach might have been suitable during the first months of the pandemic, this might no longer be the case for a longer period.To examine approaches that may better assess the use of cancer surgeries.In a cross-sectional design, the nationwide French hospital facility data (Medicalised Information System Program) were used to assess cancer surgery for 6 cancer site categories in adults from January 1, 2010, to December 31, 2021.Estimated cancer surgery activity during the COVID-19 pandemic.Three models were proposed to assess the expected number of surgical procedures between 2020 and 2021 and make a comparison with those observed in earlier years.In France, cancer removal surgeries account for approximately 7000 hospitalizations per year for liver cancer; 4000 for pancreatic cancer; 7700 for ovarian cancer; 1300 for esophagus cancer; 23 000 for ear, nose, and throat (ENT) cancer; 78 000 for breast cancer; and 16 600 for thoracic cancers. For most cancer sites, the number of surgical procedures increased from 2010 to 2019: liver, 14%; pancreas, 38%; ovary, 14%; esophagus, 18%; breast, 8%; and thoracic, 29%. Assuming stability, these values underestimate the gap in activity observed in 2020-2021. For other procedures, a decrease was observed: stomach, -10%, and ENT, -6%. Assuming stability, these values overestimate the gap in activity observed in 2020-2021. At the end of 2021, according to the model, the gap in activity observed in 2020-2021 was estimated at between -1.4% and 1.7% for breast, -6.6% and -7.3% for thoracic, -3.1% and -2.5% for ovarian, -4.2% and -1.7% for pancreas, -6.7% and 5.9% for stomach, and -13.0% and -13.9% for esophageal cancers. For ENT, liver, and urologic cancers, because the trend was different before and after 2015, it was necessary to opt for modeling using only the most recent period. The cumulative gap in activity observed in 2020-2021 was estimated at -1.0% for ENT cancers, -5.3% for liver cancers, and -2.9% for urologic cancers.The findings of this study suggest that short- and medium-term trends must be considered to estimate COVID-19 cancer surgery activities. Breast cancer is the site for which the activity showed the smallest decrease during the pandemic, with almost full recovery in 2021.
Neutrophil-activating therapy for the treatment of cancer
Authors: Ian L Linde, Tyler R Prestwood, Jingtao Qiu, Genay Pilarowski, Miles H Linde, Xiangyue Zhang, Lei Shen, Nathan E Reticker-Flynn, David Kung-Chun Chiu, Lauren Y Sheu, Simon Van Deursen, Lorna L Tolentino, Wen-Chao Song, Edgar G Engleman
Journal: Cancer Cell (2023)
Development and Validation of Esophageal Squamous Cell Carcinoma Risk Prediction Models Based on an Endoscopic Screening Program
Authors: Junming Han, Xiaolei Guo, Li Zhao, Huan Zhang, Siqi Ma, Yan Li, Deli Zhao, Jialin Wang, Fuzhong Xue
Journal: JAMA Network Open (2023)

Importance Assessment tools are lacking for screening of esophageal squamous cell cancer (ESCC) in China, especially for the follow-up stage. Risk prediction to optimize the screening procedure is urgently needed. Objective To develop and validate ESCC prediction models for identifying people at high risk for follow-up decision-making. Design, Setting, and Participants This open, prospective multicenter diagnostic study has been performed since September 1, 2006, in Shandong Province, China. This study used baseline and follow-up data until December 31, 2021. The data were analyzed between April 6 and May 31, 2022. Eligibility criteria consisted of rural residents aged 40 to 69 years who had no contraindications for endoscopy. Among 161 212 eligible participants, those diagnosed with cancer or who had cancer at baseline, did not complete the questionnaire, were younger than 40 years or older than 69 years, or were detected with severe dysplasia or worse lesions were eliminated from the analysis. Exposures Risk factors obtained by questionnaire and endoscopy. Main Outcomes and Measures Pathological diagnosis of ESCC and confirmation by cancer registry data. Results In this diagnostic study of 104 129 participants (56.39% women; mean [SD] age, 54.31 [7.64] years), 59 481 (mean [SD] age, 53.83 [7.64] years; 58.55% women) formed the derivation set while 44 648 (mean [SD] age, 54.95 [7.60] years; 53.51% women) formed the validation set. A total of 252 new cases of ESCC were diagnosed during 424 903.50 person-years of follow-up in the derivation cohort and 61 new cases from 177 094.10 person-years follow-up in the validation cohort. Model A included the covariates age, sex, and number of lesions; model B included age, sex, smoking status, alcohol use status, body mass index, annual household income, history of gastrointestinal tract diseases, consumption of pickled food, number of lesions, distinct lesions, and mild or moderate dysplasia. The Harrell C statistic of model A was 0.80 (95% CI, 0.77-0.83) in the derivation set and 0.90 (95% CI, 0.87-0.93) in the validation set; the Harrell C statistic of model B was 0.83 (95% CI, 0.81-0.86) and 0.91 (95% CI, 0.88-0.95), respectively. The models also had good calibration performance and clinical usefulness. Conclusions and Relevance The findings of this diagnostic study suggest that the models developed are suitable for selecting high-risk populations for follow-up decision-making and optimizing the cancer screening process.
Impact of Common Vitamin D–Binding Protein Isoforms on Supplemental Vitamin D<sub>3</sub> and/or Calcium Effects on Colorectal Adenoma Recurrence Risk
Authors: David Corley Gibbs, Elizabeth L. Barry, Veronika Fedirko, John A. Baron, Roberd M. Bostick
Journal: JAMA Oncology (2023)

Importance Variants in the vitamin D–binding protein (DBP) gene ( GC ) encode DBP isoforms that may affect vitamin D metabolism. However, whether these isoforms modify the effects of vitamin D 3 and/or calcium supplementation on colorectal adenoma recurrence is unclear. We hypothesized that supplementation effects may be stronger among those with the DBP2 isoform (encoded by the rs4588 *A allele), which is associated with vitamin D deficiency and modified the associations of circulating vitamin D with risk for colorectal neoplasms in observational studies. Objective To estimate supplemental vitamin D 3 and/or calcium effects on colorectal adenoma recurrence according to 3 common DBP isoforms (DBP1s, DBP1f, DBP2) encoded by 2 missense variants: rs7041 ( NG_012837 .3:g.57904T&amp;amp;gt;G NP_001191235 .1:p.Asp432Glu) and rs4588 ( NG_012837 .3:g.57915C&amp;amp;gt;A NP_001191235 .1:p.Thr436Lys). Design, Setting, and Participants Secondary analysis of a randomized, double-blind, placebo-controlled clinical trial of 2259 participants with a recently diagnosed adenoma and no remaining polyps after complete colonoscopy in the US from July 1, 2004, to August 31, 2013. The current analyses were performed from August 12, 2019, to July 16, 2022. Interventions Daily vitamin D 3 (1000 IU), calcium (1200 mg), both, or placebo. Main Outcomes and Measures One or more adenomas diagnosed during 3 to 5 years of follow-up. Treatment effects were estimated according to DBP isoform as risk ratios (RRs) and 95% CIs using Poisson regression analysis. Results Of the 2259 participants randomized (mean [SD] age, 58 [6.8] years; 1033 [64%] men), 1604 non-Hispanic White participants (chosen to avoid population stratification bias) were included in the analysis. Among those with the DBP2 isoform ( rs4588 *AC or AA), the RRs (95% CI) for adenoma recurrence were 0.84 (0.72-1.00) with vitamin D 3 relative to no vitamin D 3 , 0.83 (95% CI, 0.70-0.99) with calcium relative to no calcium, and 0.76 (95% CI, 0.59-0.98) with both agents relative to neither agent. Conversely, among those without DBP2 ( rs4588 *CC), the corresponding values were 1.08 (95% CI, 0.93-1.26; P = .03 for interaction) with vitamin D 3 relative to no vitamin D 3 , 0.98 (95% CI, 0.84-1.14; P = .37 for interaction) with calcium relative to no calcium, and 1.09 (0.88-1.36; P = .03 for interaction) with both agents relative to neither agent. Among DBP2 homozygotes ( rs4588 *AA), the RR for adenoma recurrence was 0.57 (95% CI, 0.31-1.08) with both agents relative to neither agent. Conclusions and Relevance The findings of this secondary analysis of a randomized clinical trial suggest that individuals with the DBP2 isoform–encoding rs4588 *A allele may particularly benefit from vitamin D 3 and/or calcium supplementation for colorectal adenoma prevention. Trial Registration ClinicalTrials.gov Identifier: NCT00153816